Rare inherited disorder of heme biosynthesis resulting from a partial deficiency of ferrochelatase.
30-50% deficiency of ferrochelatase activity.
Autosomal recessive inborn error of metabolism.
There is an X-linked form accounting for 2-10% of cases and results from a gain of function of erythroid specific aminolevulinic acid synthetase 2.
The disease occurs in all races and ethnic groups but it rare among blacks.
Estimated prevalence between 1 and 75,00 and 1 in 200,000 among White persons.
Massive excretion of protoporphyrin into stool.
Associated with mild to moderate photosensitivity and no hemolysis.
Associated with severe painful photosensitivity and results from accumulation of protoporphyrin in erythroid cells and tissues because of decreased activity of the heme biosynthetic that inserts iron in the protoporhyrin to form heme.
Results in overproduction of photoactive metal free protoporphyrin in the marrow and its accumulation in erythrocytes, plasma, liver, and vascular endothelium.
exposure to visible light, protoporphyrin in the vascular endothelium is photoactivated, causing, inflammation, cellular damage, and severe pain.
Photosensitivity usually manifests in early childhood and occurs 1-20 minutes after direct exposure to the sun.
Patients may develop severe skin burns, typically on the hands and face.
Patients typically present in childhood with excruciating phototoxic attacks, primarily affecting the face and dorsum of the hands, soon after sun exposure.
Neuropathic pain can be incapacitating and last several days and does not respond to analgesics.
Onset in childhood with lifelong photosensitivity with overproduction and accumulation of protoporphyrin in erythropoietic cells, erythrocytes, skin, liver and plasma.
Characteristically they were prodromal symptoms that precedes severe pain and include tingling, itching, and burning, which is a warning to limit sun exposure.
Approximately 25% of patients have prodromal symptoms within 10 minutes after sun exposure and approximately 60% of prodromal symptoms within 30 minutes.
No treatment is effective for relief of the severe pain or other symptoms as follows longer exposure, and recovery may take 2 to 7 days.
Sunlight avoidance becomes the primary mode of treatment of symptom prevention, limiting normal daily activities, and reducing quality of life.
Generally a mild disease with some carriers having only mildly elevated protoporphyrin levels without skin photosensitivity.
Patients may develop porphyrin rich gallstones.
Rarely death may be associated with hepatic insufficiency.
Protoporphyrin can damage the liver and biliary system, and fewer than 5% of patients have liver disease that leads to liver, or bone marrow transplantation.
Protoporphyrin is released from red cells into the circulation and gains access vascular endothelium and liver, and is excreted biliary tract.
Patients learn to avoid sunlight and have minimal light exposure, wear protective clothing or remain indoors.
When accumulated phototoxic protoporphyrin in the skin is exposed to sun or visible light (400-410 nm) itis activated by blue light triggering singlet oxygen free radicals reactions leading to neuropathic pain that may last for hours to days.
In about 5% of cases the protoporphyrin in transit to the liver may precipitate into gallstones and cause cholestatic hepatitis.
Cholestatic hepatitis may progress to liver failure and may be requirement for liver transplantation.
No effective therapy is available, although beta-carotene, and N-acetylene-L-cysteine and vitamin C have been used.
Photo protective clothing is beneficial.
Afamelanotide (Scenesse) is an analog of human Alpha-melanocyte-stimulating hormone and binds to the melanocyte 1 receptor in dermal cells including melanocytes and increases the production of eumelanin in the epidermis without the ultra light violet light induced cellular damage that occurs when melanin production is stimulated light ultraviolet.
Afamelanotide (Scenesse) enables patients with this illness to have more direct exposure to sunlight without pain due to phototoxicity.
Dersimelagon significantly increases the duration of symptom free sunlight exposure, in patients with the erythropoetic protoporphyria, or X linked protoporphyria.
Dersimelagon is it orally administered selective melanocortin 1 receptor agonist, that results in a photo protection, and anti-oxidative effects.